Neurosteroids: Can a 2alpha,3alpha-epoxy ring make up for the 3alpha-hydroxyl group?

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F16%3A00458613" target="_blank" >RIV/67985823:_____/16:00458613 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61388963:_____/16:00458613 RIV/00023752:_____/16:43914918

Výsledek na webu

<a href="http://dx.doi.org/10.1016/j.steroids.2015.11.007" target="_blank" >http://dx.doi.org/10.1016/j.steroids.2015.11.007</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.steroids.2015.11.007" target="_blank" >10.1016/j.steroids.2015.11.007</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Neurosteroids: Can a 2alpha,3alpha-epoxy ring make up for the 3alpha-hydroxyl group?

Popis výsledku v původním jazyce

Seven steroid epoxides were prepared from 5 alpha-pregn-2-en-20-one and 5 alpha-pregn-3-en-20-one and their side-chain derivatives. All compounds were tested in vitro for binding to gamma-aminobutyric acid (GABA(A)) receptor, some of them also in vivo for anticonvulsant action. 2 alpha,3 alpha-Epoxy-5 alpha-pregnan-20-one inhibited the TBPS binding to the GABA(A) receptor and showed a moderate anticonvulsant action in immature rats. In contrast, its 3 alpha,4 alpha-isomer was inactive. More polar epoxide derivatives, modified at the side chain were less active or inactive. Noteworthy, diol 20, the product of trans-diaxial opening of the 2 alpha,3 alpha-epoxide 4, was not able to inhibit the TBPS binding, showing that the activity of the epoxide is due to the compound itself and not to its hydrolytic product. The 3 alpha-hydroxyl group is known to be essential for the GABA(A) receptor binding. Despite the shortness of in vivo effects which are probably due to metabolic inactivation of the products prepared, our results show that the 2 alpha,3 alpha-epoxy ring is another structural pattern with ability to bind the GABA(A)R.

Název v anglickém jazyce

Neurosteroids: Can a 2alpha,3alpha-epoxy ring make up for the 3alpha-hydroxyl group?

Popis výsledku anglicky

Seven steroid epoxides were prepared from 5 alpha-pregn-2-en-20-one and 5 alpha-pregn-3-en-20-one and their side-chain derivatives. All compounds were tested in vitro for binding to gamma-aminobutyric acid (GABA(A)) receptor, some of them also in vivo for anticonvulsant action. 2 alpha,3 alpha-Epoxy-5 alpha-pregnan-20-one inhibited the TBPS binding to the GABA(A) receptor and showed a moderate anticonvulsant action in immature rats. In contrast, its 3 alpha,4 alpha-isomer was inactive. More polar epoxide derivatives, modified at the side chain were less active or inactive. Noteworthy, diol 20, the product of trans-diaxial opening of the 2 alpha,3 alpha-epoxide 4, was not able to inhibit the TBPS binding, showing that the activity of the epoxide is due to the compound itself and not to its hydrolytic product. The 3 alpha-hydroxyl group is known to be essential for the GABA(A) receptor binding. Despite the shortness of in vivo effects which are probably due to metabolic inactivation of the products prepared, our results show that the 2 alpha,3 alpha-epoxy ring is another structural pattern with ability to bind the GABA(A)R.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FH - Neurologie, neurochirurgie, neurovědy

OECD FORD obor

—

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2016

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Steroids

ISSN

0039-128X

e-ISSN

—

Svazek periodika

105

Číslo periodika v rámci svazku

Jan

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

7

Strana od-do

12-18

Kód UT WoS článku

000368219900002

EID výsledku v databázi Scopus

2-s2.0-84949519080